Galanin is a small (29-30 amino acid) neuroendocrine peptide which does not belong to any known peptide family (Bedecs et al., Int. J. Biochem. Cell. Biol. 27: 337-349 (1995)). It is widely distributed in the central nervous system and other tissues, and has been reported to have a large number of diverse biological and pharmacological activities. Galanin has been reported to: (a) promote growth hormone release (Bauer et al., The Lancet 2:192-195 (1986)); (b) inhibit glucose-induced insulin release (Ahren et al., FEBS Lett. 299:233-237 (1988)); (c) regulate motility in the gastrointestinal tract (Fox-Thelkeld et al., Gastroenter-ology 101:1471-1476 (1991)); (d) stimulate feeding behavior (Crawley et al., J. Neurosci 10:3695-3700 (1990)); and (e) impair cognitive function (Mastropaolo et al., Proc. Nat'l Acad. Sci. U.S.A. 85:9841-9845 (1988)).
Of particular pharmacological interest are galanin's analgesic effects (Post et al., Acta Physiol. Scand. 132:583-584 (1988)). In the spinal cord, galanin inhibits nociceptive reflexes and potentiates the analgesic effect of morphine (Wiesenfeld-Hallin et al. Neurosci. Lett. 105:149-154 (1989)). Target administration of galanin hyperpolarizes dorsal horn neurons and chronic administration of a galanin receptor antagonist after axotomy has been reported to markedly increase autonomy in rats (Verge et al., Neurosci. Lett. 149:193-197 (1993)). These observations indicate that galanin, like morphine, has strong anti-nociceptive actions in vivo. Thus, the known pharmacological effects of galanin suggest potential therapeutic applications as an anesthetic or analgesic in animals and humans.
Galanin exerts its effects by binding to membrane-bound receptors. The cDNA for one such receptor (“GAL-R1”) has been cloned from both humans and rats (Habert-Ortoliet et al., Proc. Natl. Acad. Sci. U.S.A. 91:9780-9783 (1994); Burgevin et al., J. Mol. Neurosci. 6:33-41 (1995)). High levels of rat GAL-R1 mRNA have been found in the ventral hippocampus, thalamus, amygdala, and medulla oblongata of the brain and in the dorsal horn of the spinal cord (Burgevin et al., supra). Pharmacological data obtained using galanin fragments, agonists and antagonists have suggested that more than one type of receptor may be responsible for galanin's actions (for a review, see Valkna et al., Neurosci. Lett. 187:75-78 (1995)). The isolation and characterization of new receptors for galanin would be highly desirable to assist in the discovery and development of therapeutic agents for altering galanin activity in vivo.